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キーワード:
Alzheimer's disease; Basal nucleus of meynert; Cholinergic fibers; 18F-fluorodeoxyglucose; Positron-emission tomography
要旨:
Cholinergic dysfunction is well known to significantly contribute to the cognitive decline in Alzheimer's disease (AD). However, it has not been clarified whether the cholinergic dysfunction is a primary event or a retrograde event secondary to neuronal loss of the cholinergic targets. Analysis of the in vivo neuronal activity of the basal forebrain in the early stages of AD could yield more information about this issue. In the present study, uptake of [18F]-fluorodeoxyglucose (FDG) in the basal forebrain was measured in 13 patients with mild cognitive impairment (MCI), 20 with early AD, and 14 healthy subjects using high-resolution research tomograph-PET. The FDG uptake was compared among the groups and correlated with the Mini Mental Status Examination (MMSE) score. The MCI patients showed significantly higher FDG uptake in the basal forebrain than the healthy subjects and the AD patients, and those did not developed dementia after 2 years showed even higher uptake than those developed dementia. The basal forebrain metabolism showed an inverted-U relationship with MMSE score in highly educated subjects, and cross-voxel analysis over the whole brain in MCI patients revealed a significant correlation in uptake between the basal forebrain and the fronto-temporal cortices. These findings indicate that in MCI patients, neuronal activity in the basal forebrain is initially increased over that in normal aging and then decreased only with further cognitive decline. The increase is consistent with a secondary compensation against neurodegeneration at target areas, and may provide brain reserve against functional impairments at incipient stages of dementia.
